Prognostic Interplay Between COVID-19 and Heart Failure With Reduced Ejection Fraction

Background: COVID-19 may negatively impact the prognosis of patients with chronic HFrEF and vice versa.

Methods: This study included 2 parallel analyses of patients in the United States who were in the TriNetX health database and who underwent polymerase chain reaction testing for SARS-CoV-2 as an inpatient or outpatient between January and September of 2020. Analysis A included patients with positive tests for COVID-19 and compared patients with histories of worsening heart failure with reduced ejection fraction (HFrEF) (hospitalization due to heart failure (HF) or IV diuretic use during the prior 12 months), HFrEF without worsening, and no prior HF. Analysis B included patients with histories of HFrEF and compared patients with positive vs negative COVID-19 tests. Outcomes included mortality and worsening HF. In both analyses, prespecified subgroup analyses were stratified by inpatient vs outpatient settings of the COVID-19 tests.

Results: In Analysis A, of 99,052 patients with positive COVID-19 tests, 514 (0.5%) and 524 (0.5%) patients had histories of worsening HFrEF and HFrEF without worsening, respectively. After adjustment, compared to patients without HF, worsening HFrEF (risk ratio [RR] 1.42, 95% CI 1.10-1.83; P< 0.001) and HFrEF without worsening (RR 1.33, 95% CI 0.96-1.84; P= 0.06) were associated with higher 30-day mortality rates. Excess risk of mortality tended to be pronounced in patients initially diagnosed with COVID-19 as outpatients (P for interaction, 0.12 and 0.006, respectively). In Analysis B, of 14,838 patients with HFrEF tested for COVID-19, 1038 (7.0%) had positive tests. After adjustment, testing positive was associated with excess 30-day mortality risk (RR 1.67, 95% CI 1.38-2.02; P< 0.001) and worsening HF (RR 1.33, 95% CI 1.17-1.51; P< 0.001). Mortality risk was nominally more pronounced among patients presenting as outpatients (P for interaction 0.07).

Conclusion: In this large cohort of patients tested for COVID-19, among patients testing positive, a history of HFrEF with or without worsening was associated with excess mortality rates, particularly among patients diagnosed with COVID-19 as outpatients. Among patients with established HFrEF, compared with testing negative, testing positive for COVID-19 was independently associated with higher risk of death and worsening HF.